Hypoxia-inducible factor 1α inhibits the fibroblast-like markers type I and type III collagen during hypoxia-induced chondrocyte redifferentiation: Hypoxia not only induces type II collagen and aggrecan, but it also inhibits type I and type III collagen in the hypoxia-inducible factor 1α-dependent redifferentiation of chondrocytes
| العنوان: | Hypoxia-inducible factor 1α inhibits the fibroblast-like markers type I and type III collagen during hypoxia-induced chondrocyte redifferentiation: Hypoxia not only induces type II collagen and aggrecan, but it also inhibits type I and type III collagen in the hypoxia-inducible factor 1α-dependent redifferentiation of chondrocytes |
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| المؤلفون: | Karim Boumediene, Jean-Marc Elissalde, Elise Duval, Philippe Galéra, Magali Demoor, Sylvain Leclercq |
| المصدر: | Arthritis & Rheumatism. 60:3038-3048 |
| بيانات النشر: | Wiley, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Adult, medicine.medical_specialty, Immunology, Type II collagen, Collagen Type I, Chondrocyte, Chondrocytes, Rheumatology, Internal medicine, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Aggrecans, Fibroblast, Collagen Type II, Cells, Cultured, Aggrecan, Aged, Aged, 80 and over, Chemistry, Cartilage homeostasis, Cell Differentiation, SOX9 Transcription Factor, Middle Aged, Hypoxia-Inducible Factor 1, alpha Subunit, Chondrogenesis, Cell Hypoxia, Cell biology, Collagen Type I, alpha 1 Chain, Collagen Type III, medicine.anatomical_structure, Endocrinology, Hypoxia-inducible factors, Ectopic expression, Collagen |
| الوصف: | Objective Autologous chondrocyte implantation requires expansion of cells ex vivo, leading to dedifferentiation of chondrocytes (loss of aggrecan and type II collagen to the profit of type I and type III collagens). Several approaches have been described for redifferentiation of these cells. Among them, low oxygen tension has been exploited to restore the differentiated chondrocyte phenotype, but molecular mechanisms of this process remain unclear. However, under conditions of hypoxia, one of the major factors involved is hypoxia-inducible factor 1alpha (HIF-1alpha). The purpose of this study was to investigate the role of HIF-1alpha during human chondrocyte redifferentiation. Methods We used complementary approaches to achieving HIF-1alpha loss (inhibition by cadmium ions and dominant-negative expression) or gain (ectopic expression and cobalt ion treatment) of function. Expression of chondrocyte, as well as fibroblast-like, phenotype markers was determined using real-time reverse transcription-polymerase chain reaction and Western blot analyses. Binding activities of HIF-1alpha and SOX9, a pivotal transcription factor of chondrogenesis, were evaluated by electrophoretic mobility shift assays and by chromatin immunoprecipitation assay. Results We found that hypoxia and HIF-1alpha not only induced the expression of SOX9, COL2A1, and aggrecan, but they simultaneously inhibited the expression of COL1A1, COL1A2, and COL3A1. In addition, we identified the binding of HIF-1alpha to the aggrecan promoter, the first such reported demonstration of this binding. Conclusion This study is the first to show a bimodal role of HIF-1alpha in cartilage homeostasis, since HIF-1alpha was shown to favor specific markers and to impair dedifferentiation. This suggests that manipulation of HIF-1alpha could represent a promising approach to the treatment of osteoarthritis. |
| تدمد: | 1529-0131 0004-3591 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::beb2d979a87cfdb72433050e53a9fd45Test https://doi.org/10.1002/art.24851Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....beb2d979a87cfdb72433050e53a9fd45 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15290131 00043591 |
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